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04 46201 408-431 梶波 3/柴.Indd The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Original Article J Atheroscler Thromb, 2019; 26: 408-431. http://doi.org/10.5551/jat.46201 Real-World Data to Identify Hypercholesterolemia Patients on Suboptimal Statin Therapy Kouji Kajinami1, Asuka Ozaki2, Yuki Tajima2, Shizuya Yamashita3, 4, Hidenori Arai5 and Tamio Teramoto6 1Department of Cardiology, Kanazawa Medical University, Ishikawa, Japan 2Sanofi, Tokyo, Japan 3Rinku General Medical Center, Osaka, Japan 4Department of Community Medicine & Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan 5National Center for Geriatrics and Gerontology, Aichi, Japan 6Teikyo Academic Research Center, Tokyo, Japan Aim: Statins are generally well-tolerated but some patients develop adverse events and down-titrate or discon- tinue statins. It is important to understand the frequency of dyslipidemia patients with the inability to continue statins. The aim of the present study was to identify the frequency of high-risk dyslipidemia patients who are unable to take or not taking statins for any reason using Japanese hospital claims database. Methods: 2,527,405 dyslipidemia patients with atherosclerotic cardiovascular disease were investigated between April 2008 and September 2017. Definition 1 included statin discontinuation or down-titration with non-statin lipid modifying therapy (LMT) prescription, rhabdomyolysis or muscle-related symptoms with statin down- titration or discontinuation, or prescription for ≥3 statin types. Definition 2 included all components of Defini- tion 1 in addition to statin down-titration or discontinuation for any reason. Patients never given statins but who started non-statin LMT were considered as Definition 3. The achievement rate of the target LDL-C level was investigated. Results: Among 54,296 patients with statin prescription, 2.32% and 48.38% patients were identified as Defini- tion 1 and 2, respectively. Of eligible patients, 13.16% patients were identified as Definition 3. The achievement rate of target LDL-C level was lower in patients meeting each definition than not satisfying each definition. Conclusions: There is a proportion of high-risk dyslipidemia patients unable to take or not taking statins for any reason, and it is associated with lower achievement rates of target LDL-C levels. Suboptimal management of LDL-C is directly associated with residual cardiovascular risk and implementation of alternative therapeutic options in addition to existing LMT is warranted. See editorial vol. 26: 403-405 Key words: Hypercholesterolemia, Claim data, Statin, Non-HDL-cholesterol, LDL-cholesterol major cause of mortality in Japan and worldwide1, 2). Introduction The Japan Atherosclerosis Society (JAS) guidelines rec- Lowering low-density lipoprotein cholesterol (LDL- ommend lowering LDL-C to ＜100 mg/dL in patients C) level is one of the most widely available approaches to with a history of CAD and to ＜70 mg/dL (or by 50% prevent atherosclerotic cardiovascular disease (ASCVD), or more) in high-risk patients with heterozygous famil- including coronary artery disease (CAD), which is a ial hypercholesterolemia or acute coronary syndrome Address for correspondence: Kouji Kajinami, Department of Cardiology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan E-mail: [email protected] Received: August 1, 2018 Accepted for publication: September 20, 2018 Copyright©2019 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License. 408 Dyslipidemia on Suboptimal Statins for secondary prevention of CAD3). using a Japanese electrical medical record (EMR) data- The JAS guidelines as well as those of other major base. Because lipid management in these patients might international associations including the American Col- be poor, we also investigated the frequency of patients lege of Cardiology/American Heart Association (ACC/ who achieved target values such as LDL-C recommended AHA), the European Society of Cardiology/European by the JAS guidelines3). Atherosclerosis Society, the National Lipid Association, and the International Atherosclerosis Society recom- Methods mend statins as the first-line treatment for dyslipidemia patients with elevated LDL-C levels4-7). Asian patients Database often show an increased response to drug therapy com- This retrospective observational study was con- pared to Western populations, leading to lowered doses ducted using the EBM Provider, which contains hos- of therapeutic drugs such as statins. The approved max- pital claims database stored in electronic hospital infor- imum dose of statin is lower (e.g., atorvastatin 40 mg/ mation systems constructed by Medical Data Vision day and rosuvastatin 20 mg/day) as well as clinically Co., Ltd. (MDV; Tokyo, Japan). The EBM Provider used dose8, 9). Statins are generally well tolerated, and covers approximately 20.8 million patients from 323 serious adverse events are infrequent10, 11); however, some hospitals across Japan (as of December 2017) with bed patients experience statin-associated muscle symptoms numbers ranging from 20 to over 1000. This database (SAMS) such as myositis and rhabdomyolysis and hepatic also includes approximately 19% of all acute phase disorder that result in dose reductions or discontinua- hospitals in Japan, including university hospitals, which tion of statin treatment 4-7, 12). The inability to continue use the Diagnostic Procedure Combination (DPC) pay- an effective dosage or the discontinuation of a statin ment system/Per-Diem Payment System. treatment may limit clinically important effects, such The EBM Provider includes anonymized patient- as CAD risk reductions13, 14). level information on sex, age, previous medical history Statin intolerance is a term that is widely used to (diagnosed diseases), medical procedure, and prescribed describe clinical phenomenon such as the inability to drug. Laboratory test values were also provided by 35 continue an effective dosage or the discontinuation of hospitals. Information about the diagnosis and drugs statin treatment due to adverse events, but there are no is extractable based on the International Classification globally accepted criteria for statin intolerance. Previ- of Disease (ICD)-10 codes and the Anatomical Thera- ous studies have attempted to estimate the proportion peutic Chemical (ATC) code, respectively. of dyslipidemia patients unable to continue an effec- tive dosage or who need to discontinue statin treat- Patient Selection ment using various criteria; results range from 1% to All patients diagnosed with ASCVD (ICD-10 30%15, 16). With the complexity of a dose-dependent code: I20, I21, I22, I23, I24, I25, I63, I65, I66, I67, relationship of adverse effects and more sensitive response I69, I70, I71, I72, I73, I74) between April 2008 and in the Asian population to medications, the precise September 2017 (defined as the study period) were iden- number of the inability to continue an effective dos- tified from the EBM Provider database. Patients who age or the discontinuation of statin treatment due to met all of the following criteria were included in the adverse events is unknown. present study: 1) diagnosis of dyslipidemia (standard- In an era of new alternative lipid-lowering thera- ized Japanese disease codes: 2724036; high LDL cho- pies supported by emerging evidence, it is important lesterolemia, 2720004; hypercholesterolemia, 8840108; to understand the frequency of dyslipidemia patients essential hypercholesterolemia, 8833881; mixed hyper- with an inability to continue an effective dosage of lipidemia, 2724007; hyperlipidemia, 8833722; hyper- statins by quantifying patients with high cardiovascu- lipoproteinemia, 8844446; dyslipidemia, 2724012; essen- lar risk who may be candidates for non-statin lipid- tial hyperlipidemia, 2729002; disorder of lipid metab- modifying therapy (LMT) such as PCSK9 inhibitors, olism, 8845052; type1 diabetic hypercholesterolemia, cholesterol absorption inhibitors, and fibrates in Japan. 8845081; type2 diabetic hypercholesterolemia, 8838067; diabetic hypercholesterolemia) during the study period; 2) initiation of any statin (ATC code: C10A1, C11A1) Aim agents during the study period and initiation of non- The aim of the present study was to identify the statin LMT (ATC code: C10, C11) if statin agents were frequency of dyslipidemia patients with a history of not prescribed during the study period (as an index ASCVD such as CAD with an inability to continue date); 3) at least 365 days of medical data available an effective dosage or who need to discontinue statin before and after the index date; 4) age at the index date treatment for any reason in Japanese clinical practice over 20 years; 5) no prescription of LMT during the 409 Kajinami et al. look-back period of 365 days before the index date; each comparator. The earliest LDL-C and non-high- and 6) diagnosis of ASCVD before the index date. density lipoprotein (HDL-C) level recorded 365 days Patients with age at the index date younger than 20 after the index date were used. The target value of each years old and index date before April 2009 or after laboratory test parameter was referred the value of a September 2016 were excluded from the study. patient with a history of CAD recommended by the Definition of dyslipidemia patients who were un- JAS guidelines (LDL-C:
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